Plavix-popping patients in posession of a particular gene that prevents its proper metabolism were at twice the risk of sustaining cardiovascular events, and the risk could not be mitigated by high doses of the stuff, according to 2 studies presented at last week’s meetings of the American College of Cardiology.
In the first study, Paul Gurbel and colleagues showed that 21% of patients with the cytochrome P450 2C19*2 polymorphism had a cardiovascular event within a year following coronary artery stenting, even though they received Plavix to prevent such occurrences.
The University of Maryland-based scientists found that only 10% of noncarriers experienced that outcome.
“This common variant encodes a defective enzyme that likely fails to convert Plavix to its active metabolite, leading to lesser inhibition of platelet function and diminished cardiovascular protection,” Gurbel told MedPageToday.
In the second study of 33 patients that had a poor response to the standard 75 mg dose of Plavix, Jean-Philippe Collet and colleagues at INSERM in Paris found that doubling the standard dose improved results in all but 7 patients.
Six of these 7 patients were CYP2C19*2 positive.
The scientists prescribed Effient, an alternative antiplatelet drug to eligible patients in this group, and all responded nicely.
“The day is rapidly approaching” when physicians can determine in advance how patients will respond to antiplatelet therapy and select agents likely to be effective “rather than blindly administering Plavix as we do now,” Gurbel concluded.
Plavix is co-marketed by Sanofi-Aventis and Bristol-Meyers Squibb. It is the world’s second largest selling drug, with $4 plus billion in revenues last year. It enjoys patent protection until November, 2011.
Eli Lilly and Daiichi Sankyo co-developed Effient, which was recently approved in the EU and is edging toward FDA approval.